Atrial natriuretic factor is secreted from atrial myocytes in response to various stimuli: atrial strech, tachycardia, pressor hormones, opiates, etc. In our studies we addressed 2 questions, 1) Whether the hypophysis is involved in ANF release, as suggested by some investigators, 2) Whether atrial appendectomy, thus removing the main source of ANF, alters its' release to different stimuli. We used hypophysectomized rats and applied 1) a chronic stimulus for ANF release by placing an aortocaval fistula which causes high output heart failure and chronic volume overload, and 2) an acute stimulus in the form of rapid atrial pacing of 500 beats/minute for 5 minutes. In both types of stimuli we found a marked increase of plasma ANF to a similar level as in control rats. In conscious, chronic atrial-appendectomized rats we applied 1) acute volume expansion, 2) salt load, and 3) norepinephrine as acute stimuli as well as an aortocaval fistula for a chronic stimulus. We found a differential response, the one to acute volume expansion was severely blunted, as reported in the literature, whereas the other acute stimuli and the chronic stimulus elicited a normal increase in plasma ANF. We conclude that: 1) Hemodynamic factors are the important determinants of ANF release 2) no hypophyseal factor is required and 3) removing the atrial appendages does not preclude a normal ANF response to different stimuli.